Intro to chemotherapy Flashcards
why is chemotherapy unique?
- selective toxicity
- selects for resistant strains
- hypersensitivity and organ directed
- lowers the microorganism load for the host defense
what is the problem with hypersensitivity and organ directed class of drugs?
toxicity
what to do to prevent the development of resistance when taking abx?
reach and maintain ADEQUATE BLOOD LEVELS
Is maintenance of constant blood levels more important in bacteriostatic or bactericidal?
BACTERIOSTATIC than bactericidal agents
what are mechanisms for drug resistant strains leading ineffectiveness?
- fails to absorb drug
- inactivate drug
- pump out drug
- target is modified
- increased production of target
- altered metabolic pathway bypass target
how is antimicrobial resistance acquired?
vertical
horizontal
what is vertical transfer?
to daughter cells by a mutation
what is horizontal transfer?
from a donor cell of another bacterial species:
- transduction
- transformation
- conjugation
how does transduction occur?
via bacteriophages
how does transformation occur?
via incorporation of free DNA
how does conjugation occur?
transfer of genes thru sex pilus
what is the status of Penicillin resistant strains of pnemococci?
> 50% in Europe and rising in US
there is a worldwide emergence of Haemophilus and gonococci that are different. how diff?
produce b-lactamase
where is MRSA?
hospitals —NOT community-acquired infections
new strains of what bacteria are resistant to all known drugs?
enterococci, pseudomonas, enterobacters
epidemics of multiple drug resistant strains of what bacteria in US?
M. tuberculosis
what are adverse effects of antimicrobial therapy?
- over extension of pharmacologic action
- organ directed toxicity
- hypersensitivity rxn
what are types of toxicity to host?
hepatotoxicity renal ototoxicity hemopoietic visual allergies idiosyncrasies
what is empirical antimicrobial therapy?
antimicrobial agents used BEFORE the pathogen is identified. Choices depends on host factors.
what are 2 antibiotic susceptibility?
bactericidal or bacteriostatic
what is bacteriCIDAL?
cell death —think suiCIDAL
what is bacterioSTATIC?
growth inhibition—think static, NOT DYNAMIC
what is the difference in inhibitory concentration in bactericidal vs. bacteriostatic?
inhibitory concentrations are much lower that bactericidal
what is chloramphenicol?
bacteriCIDAL against Pneumococci, Meningococci, Haemophilus flu.
what is MIC?
minimum Inhibitory conc.
what is MBC?
minimum Bactericidal conc.
what are 2 types of bactericidal agents ?
concentration (drug concentration)
vs.
time (time of exposure)
dependent killing
what does concentration DK mean?
the more given the more killing
what does time DK mean?
the more you wait the more killing (time of exposure)
what does time DK mean?
killing not increased if you give more
what is PAE?
persistent suppression of bacterial growth after limited exposure to an antimicrobial agent
why is in vivo PAE LONGER than in vitro PAE ?
postantibiotic leukocyte enhancement
what is synergism?
inhibitory/killing effects of two or more antimicrobials used together are SIGNIFICANTLY GREATER (2+2=7)
what are synergism mechanisms?
- blockage of metabolic steps
- inhibition of enzymatic inactivation
- enhancement of uptake
how does TMP-SMX synergism work?
blockade of metabolic steps
how does beta-latamase inhibitors synergism work?
inhibition of enzymatic inactivation
how does penicilins synergism work?
increase uptake of aminoglycosides
how does amphotericin B synergism work?
increase uptake of flucytosine by fungi
for what infections therapeutic effect is improved when using pencilin + aminoglycoside?
enterococcal endocarditis & pseudomonas infections
for what infections therapeutic effect is improved when using doxycycline + rifampin/aminoglycoside?
brucellosis
for what infections therapeutic effect is improved when using bismuth+metronidazole+tetracycline?
H. pylori
for what infections therapeutic effect is improved when using ampicillin + aminoglycoside?
listeria
preventing resistance for what bacteria when using INH + rifampin ?
M. tuberculosis
preventing resistance for what bacteria when using gentamicing + carbenicillin?
p. aeruginosa
what are two major mechanism of antagonism?
- inhibition of bactericidal by bacteriostatic agents
2. induction of enzymatic inactivation
what are misuse of antibacterial agents leading to failure?
- untreatable infections
- fever of undetermined origin
- improper dosage
- improper duration
heard of superinfections?
YES! they are new infections that develop during chemotherapy of a PRIMARY ONE and most frequently observed with BROAD SPECTRUM ANTIBIOTICS use
what is most common superinfection?
intestinal candidiasis
what to do with intestinal candidiasis?
DON’T panic! it is fungal, continue abx, add oral nystatin or amphotericin B
What to do with staph. enterocolitis?
Stay calm…it is LIFE-THREATENING though , discontinue abx, treat with oral vancomycin
what do you pseudomembranous colitis?
it is also LIFE-THREATENING, keep calm and discontinue abx, treat with oral metronidazole or vancomycin, if SEVERE add fluids, electrolytes, conticosteroids
what is the cause of pseudomembranous colitis?
c. difficile (difficult to grow)
antibacterial prophylaxis?
umm…if efficacy proven & benefits outweigh risk
